Smoldering Multiple MyelomaPhase 2ASCENTNCT03289299
Aggressive Smoldering Curative Approach Evaluating Novel Therapies and Transplant
A Phase 2 study testing Carfilzomib, Lenalidomide and Daratumumab in people with Smoldering Multiple Myeloma, run by International Myeloma Foundation at 10 sites in United States.
Trial summary
This study evaluates the use of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Subjects will receive treatment in 3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles). Each cycle is 28 days. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Smoldering Multiple Myeloma
- What is being tested?
- Carfilzomib, Lenalidomide and Daratumumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 10 sitesUnited States
- Study dates
- 25 May 2018to 15 Nov 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years and ≤ 80 years
- High risk smoldering myeloma, which is untreated, as defined by either of the two following criteria:
- Presence of any two of the following: Serum M spike > 2 gm/dL OR an involved to uninvolved free light chain (FLC) ratio > 20 OR bone marrow PC% > 20%
- Total score of 9 or above using the following scoring system:
- FLC Ratio >10-25 = 2 >25-40 = 3 > 40 = 5
- Serum M Protein (g/dL) >1.5-3 = 3 >3 = 4
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- BMPC% >15-20 = 2 >20-30 = 3 >30-40 = 5 >40 = 6
- FISH abnormality (t(4,14), t(14,16), 1q gain, or del13q = 2
- The following laboratory values obtained 14 days prior to registration.
- Calculated creatinine clearance (using Cockcroft-Gault equation below)* ≥ 30 mL/min
- Absolute neutrophil count (ANC) ≥ 1000/mm3 (without the use of growth factors)
- Platelet count ≥ 75000/mm3
- Hemoglobin ≥8.0 g/dL
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN
- left ventricular ejection fraction (LVEF) ≥ 40%
- LVEF ≥ 40%
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 (Appendix VII)
- Previously untreated.
- Provide informed written consent.
- Negative pregnancy test done ≤14 days prior to cycle 1 day 1, for women of childbearing potential only.
- All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS®) program and be willing and able to comply with the requirements of the REMS® program.
- Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
- Willing to follow strict birth control measures as outlined in the protocol.
- Female subjects: If they are of childbearing potential, agree to one of the following:
- Practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of trial drug, AND must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
- Male subjects: even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
- Agree to practice effective barrier contraception during the entire trial treatment period and through 90 days after the last dose of trial drug, OR
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
- Willing to return to enrolling institution for follow-up during the Active Treatment Phase of the trial.
- Male subjects must agree not to donate sperm for at least 90 days after the last dose of study treatment.
- Willing to provide samples for planned research
- Life expectancy > 6 months
- Able to take aspirin (325 mg) daily as prophylactic anticoagulation. Subjects intolerant to aspirin may use warfarin or low dose molecular weight heparin, novel oral anticoagulants, or low dose molecular weight heparin
Who cannot join
- monoclonal gammopathy of undetermined significance (MGUS), standard risk smoldering myeloma, active myeloma by current IMWG definition, light chain amyloidosis with organ involvement or patients with extramedullary disease.
- Diagnosed or treated for another malignancy ≤ 2 years before trial enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. NOTE: Subjects with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- If any of the following exist at screening, subject will not be eligible for trial because this trial involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception (per protocol)
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- Other co-morbidity which would interfere with subject's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease.
- Other concurrent chemotherapy, or any ancillary therapy considered investigational. NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment.
- Peripheral neuropathy ≥ Grade 3 on clinical examination or grade 2 with pain within 30 days prior to C1D1.
- Major surgery ≤14 days prior to C1D1.
- Evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within the past 6 months. Note: Prior to trial entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
- New York Heart Association (NYHA) II, III, IV heart failure
- Known human immunodeficiency virus (HIV) positive.
- Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
- Known or suspected active hepatitis C infection.
- Any medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- Prior radiation therapy for bony lesions or plasmacytomas
- Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure), or known sensitivity to mammalian-derived products. Known allergies, hypersensitivity, or intolerance to trial drugs.
- Inability to comply with protocol/procedures.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
University of Maryland Medical Center
Baltimore, Maryland, 21201
Levine Cancer Institute
Charlotte, North Carolina, 28204
University of Chicago Medical Center
Chicago, Illinois, 60637
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Weill Cornell Medicine
New York, New York, 10022
Mayo Clinic
Rochester, Minnesota, 55905
Swedish Cancer Institute
Seattle, Washington, 98104
Moffitt Cancer Center
Tampa, Florida, 33612
University of Kansas Cancer Center
Westwood, Kansas, 66205
About this study
Official title: Aggressive Smoldering Curative Approach Evaluating Novel Therapies (ASCENT): A Phase 2 Trial of Induction, Consolidation, and Maintenance in Subjects With High Risk Smoldering Multiple Myeloma (SMM)
This study evaluates the use of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Subjects will receive treatment in 3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles). Each cycle is 28 days.
Read the detailed description
This study is a multi-center phase 2 study of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Myeloma remains incurable with the current approaches. The typical natural history of myeloma is one of repeated relapses, accompanied by genetic evolution and development of new abnormalities, which are often responsible for drug resistance. The presence of a precursor phase of smoldering myeloma, and the ability to identify those at the highest risk of progression, sets the stage to examine the possibility that we can cure the disease through early intervention. In order to potentially achieve this, we need to develop a highly effective combination that includes the most active drugs from different classes. Carfilzomib in combination with lenalidomide and dexamethasone results in high response rates and deep responses in subjects with newly diagnosed myeloma. Daratumumab in combination with lenalidomide results in high response rates in relapsed refractory disease. All these drugs are well tolerated and subjects are able to stay on them long term as a maintenance treatment. The combination of the carfilzomib, lenalidomide, daratumumab and dexamethasone presents the potential to enhance the effectiveness of the regimens. We hypothesize that this combination will lead to deep response including a higher proportion of minimal residual disease (MRD) negative disease among those with high risk smoldering myeloma and may translate into cure or long term disease quiescence.
- Conditions
- Smoldering Multiple Myeloma
- Being tested
- Carfilzomib, Lenalidomide, Daratumumab, Dexamethasone
- Keywords
- myeloma, MRD, smoldering
- Medical subject headings
- Smoldering Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
56 mg/m2 IV given on days 1, 8, and 15 of each cycle during induction and consolidation phases of the study.
LenalidomideDrug
25 mg po given on days 1-21 of each cycle during the induction and consolidation phases.
10 mg po given on days 1-21 of each cycle during the maintenance phase.
DaratumumabDrug
16 mg/kg IV given on days 1, 8, 15, and 22 of cycles 1-2; days 1 and 15 of cycles 3-6; day 1 of cycle 7-12; Day 1 of odd cycles for cycles 13-24.
DexamethasoneDrug
40 mg oral given on days 1, 8, 15, and 22 of cycles 1-6 20 mg oral given on days 1, 8, 15, and 22 of cycles 7-12
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Non-high dose treatment in 3 phases Induction 6 cycles: carfilzomib, lenalidomide, daratumumab, dexamethasone Consolidation 6 cycles: carfilzomib, lenalidomide, daratumumab, dexamethasone Maintenance 12 cycles: lenalidomide, daratumumab Receives: Drug: Carfilzomib; Drug: Lenalidomide; Drug: Daratumumab; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stringent complete response rate
A confirmed sCR on 2 consecutive evaluations at any time during the course of treatment.
Measured: During treatment
Secondary outcomes (5)
MRD negativity after each treatment phase
MRD negativity after induction, consolidation, and maintenance
Measured: 6 months, 12 months, and 2 years
MRD negativity at 1 year post treatment
Persistent MRD negativity rate will be evaluated at 1 year after completion of planned treatment consisting of induction, consolidation, and maintenance.
Measured: 1 year post treatment
Overall Survival
time of registration to death due to any cause
Measured: up to 10 years post registration
Progression-free survival
the time from registration to the earliest date of documentation of disease progression or death due to any cause
Measured: up to 10 years post registration
Adverse events
all eligible subjects that have initiated treatment will be considered evaluable for assessing adverse even rates. The maximum grade for each type of adverse event will be recorded. Relationship to trial treatment will be taken into consideration.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2017
- Study start25 May 2018
- Primary completion26 Sep 2023
- Study completion15 Nov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Smoldering Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Subjects will receive treatment in 3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles).
- Masking
- None (open label)
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Myeloma Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shaji Kumar, MD, Principal investigator, Mayo ClinicBrian Durie, MD, Principal investigator, International Myeloma Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03289299
- Sponsor's protocol ID
- BS001
- Other IDs
- 20159417, 54767414MMY2009, RV-CL-MM-IMF-008479
- Acronym
- ASCENT
- Status last verified
- Dec 2023
- First submitted
- 18 Sep 2017
- Last updated
- 12 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aggressive Smoldering Curative Approach Evaluating Novel Therapies (ASCENT): A Phase 2 Trial of Induction, Consolidation, and Maintenance in Subjects With High Risk Smoldering Multiple Myeloma (SMM)
- ClinicalTrials.gov ID
- NCT03289299
- Acronym / sponsor ID
- ASCENT / BS001
- Conditions
- Smoldering Multiple Myeloma
- Keywords
- myeloma, MRD, smoldering
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 87 participants (actual)
- Lead sponsor
- International Myeloma FoundationUniversity, hospital or other
- Collaborators
- Amgen, Janssen Scientific Affairs, LLC, Celgene, Trevie, Inc.
- Study start
- 25 May 2018 (actual)
- Primary completion
- 26 Sep 2023 (actual)
- Study completion
- 15 Nov 2031 (estimated)
- First posted
- 20 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the use of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Subjects will receive treatment in 3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles). Each cycle is 28 days.
Detailed description
This study is a multi-center phase 2 study of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Myeloma remains incurable with the current approaches. The typical natural history of myeloma is one of repeated relapses, accompanied by genetic evolution and development of new abnormalities, which are often responsible for drug resistance. The presence of a precursor phase of smoldering myeloma, and the ability to identify those at the highest risk of progression, sets the stage to examine the possibility that we can cure the disease through early intervention. In order to potentially achieve this, we need to develop a highly effective combination that includes the most active drugs from different classes. Carfilzomib in combination with lenalidomide and dexamethasone results in high response rates and deep responses in subjects with newly diagnosed myeloma. Daratumumab in combination with lenalidomide results in high response rates in relapsed refractory disease. All these drugs are well tolerated and subjects are able to stay on them long term as a maintenance treatment. The combination of the carfilzomib, lenalidomide, daratumumab and dexamethasone presents the potential to enhance the effectiveness of the regimens. We hypothesize that this combination will lead to deep response including a higher proportion of minimal residual disease (MRD) negative disease among those with high risk smoldering myeloma and may translate into cure or long term disease quiescence.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Subjects will receive treatment in 3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles).
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Carfilzomib, Drug: Lenalidomide, Drug: Daratumumab, Drug: DexamethasoneNon-high dose treatment in 3 phases Induction 6 cycles: carfilzomib, lenalidomide, daratumumab, dexamethasone Consolidation 6 cycles: carfilzomib, lenalidomide, daratumumab, dexamethasone Maintenance 12 cycles: lenalidomide, daratumumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- Age 18 years and ≤ 80 years
- High risk smoldering myeloma, which is untreated, as defined by either of the two following criteria:
- FLC Ratio >10-25 = 2 >25-40 = 3 > 40 = 5
- Serum M Protein (g/dL) >1.5-3 = 3 >3 = 4
- BMPC% >15-20 = 2 >20-30 = 3 >30-40 = 5 >40 = 6
Key exclusion criteria (19 listed)
- monoclonal gammopathy of undetermined significance (MGUS), standard risk smoldering myeloma, active myeloma by current IMWG definition, light chain amyloidosis with organ involvement or patients with extramedullary disease.
- Diagnosed or treated for another malignancy ≤ 2 years before trial enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. NOTE: Subjects with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- If any of the following exist at screening, subject will not be eligible for trial because this trial involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- Other co-morbidity which would interfere with subject's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease.
- Other concurrent chemotherapy, or any ancillary therapy considered investigational. NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carfilzomib56 mg/m2 IV given on days 1, 8, and 15 of each cycle during induction and consolidation phases of the study. | Drug | Arm A |
| Lenalidomide25 mg po given on days 1-21 of each cycle during the induction and consolidation phases. 10 mg po given on days 1-21 of each cycle during the maintenance phase. | Drug | Arm A |
| Daratumumab16 mg/kg IV given on days 1, 8, 15, and 22 of cycles 1-2; days 1 and 15 of cycles 3-6; day 1 of cycle 7-12; Day 1 of odd cycles for cycles 13-24. | Drug | Arm A |
| Dexamethasone40 mg oral given on days 1, 8, 15, and 22 of cycles 1-6 20 mg oral given on days 1, 8, 15, and 22 of cycles 7-12 | Drug | Arm A |
Primary outcome
Stringent complete response rate
Time frame: During treatment
A confirmed sCR on 2 consecutive evaluations at any time during the course of treatment.
5 secondary outcomes
MRD negativity after each treatment phase
Time frame: 6 months, 12 months, and 2 years
MRD negativity at 1 year post treatment
Time frame: 1 year post treatment
Overall Survival
Time frame: up to 10 years post registration
Progression-free survival
Time frame: up to 10 years post registration
Adverse events
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shaji Kumar, MD principal investigator
Mayo Clinic
Brian Durie, MD principal investigator
International Myeloma Foundation
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carfilzomib, Lenalidomide and Daratumumab in people with Smoldering Multiple Myeloma, run by International Myeloma Foundation at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stringent complete response rate (time frame: During treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2023.